Protein arginine methylation is an abundant post-translational modification that is involved in signal transduction and nuclear transport. The overall goal of this project is to understand the function and regulation of protein arginine methylation by determining the structures of protein arginine methyl transferases (PRMTs) alone and in complex with substrate and/or regulatory proteins. There are many indications that PRMTs may play important and diverse biological roles: (1) the high degree of conservation among different organisms, (2) the presence of at least three family members in mammals, (3) the expression of the protein in many different tissues with both nuclear and cytoplasmic forms, (4) numerous substrates that are involved in important cellular processes, and (5) the interaction of PRMT with upstream regulators. Specifically, the Principal Investigator proposes to determine the structures of (1) rat PRMT 3, (2) rat PRMT 3, peptide substrate, and AdoHcy (reaction product) complex, (3) multimeric yeast protein arginine methyltransferase, (4) rat PRMT 1 and hnRNP A1 (protein substrate), and (5) rat PRMT 1 and upstream regulator complex. In addition, he will characterize the substrate preference for different PRMTs, and possibly uncover novel biological substrates for PRMTs. The potential catalytic and sequence recognition regions of PRMT will be confirmed by mutational analysis.